Uncontrolled bleeding occurs in many situations, including severe nosebleeds, post-partum hemorrhage (PPH), trauma, dental procedures, and bleeding in patients with hemophilia. The primary concern during severe bleeding is quickly controlling blood loss, although controlling secondary bleeding, infection, and tissue repair is also important. Delivery of appropriate therapeutics, such as coagulants, anti-fibrinolytics, antimicrobials, or growth factors to the damaged vasculature can help. However, delivering such agents via systemic injections or via intravascular catheter is often not possible, particularly if the person is far from an advanced clinical setting. Topical delivery is limited by the difficult biophysical problem of moving agents upstream through blood flow and deep enough into an area of bleeding where they could treat the leaking vessels. Severe hemorrhaging is often fatal because coagulants are not able to reach and clot blood at the level of damaged vessels.
Propelled particle systems have been previously proposed for drug delivery.1-6 Some of these particles rely on gas generation and bubble propulsion to create their velocity. Such particles may contain metal catalysts that convert hydrogen peroxide dissolved in aqueous solution to oxygen gas. Other examples convert hydrogen ions in strongly acidic solutions (pH<1) to a hydrogen gas. Thus, the “fuel” for propulsion or a necessary reactant is placed in the environment of the particle and is not present in the particle itself. Mechanisms such as ultrasound or magnetically-driven swimmers for propulsion have also been proposed.7,8 
Particles that employ gas/bubble propulsion have not been used in vivo because they rely on having a “fuel” (e.g., hydrogen peroxide) which is toxic or a required reactant (i.e., a strong acid) dispersed in the living environment. Also, they generally propel at velocities many orders of magnitude slower than blood flow. 1,4 
Despite drawbacks with regard to in vivo use, progress has been made in the design of particles generally capable of functioning as microjet engines or “rockets” such as rolled microtubes, including conical versions of microtubes3,5,12. Polymer components and/or layers in such particles may be adapted for carrying drugs as well as for insulating a carrier from a reactant or “fuel” such as hydrogen peroxide, until such time as a barrier layer dissolves.
Independent from development of propelled particles are the advances that have been made in drug microcarriers. Various microparticles are known for use in carrying biologically active substances to enhance delivery to target cells, tissues, etc. Microparticles, including porous versions thereof that are made of polyelectrolytes and are capable of adsorption of biologically active materials have, been developed for drug delivery. Examples of such particles have been made by crystallizing inorganic salts such as calcium carbonate.
Also, processes for controlled fabrication of films and particles have been developed, including ones which allow for precise control of film or particle shell thickness (i.e., nanoporous template-assisted layer-by-layer (ELbL) protocols).
Volodkin et al.9 describe production of porous CaCO3 (vaterite) particles with a size distribution from 4 to 6 μm that encapsulate proteins that are adsorbed to the particles. Such particles were found to be biocompatible and decomposable at neutral pH.
Compositions comprising metal carbonates and organic acids that effervesce in contact with aqueous media have been disclosed as additives for collection devices containing bodily fluids (U.S. Pat. No. 6,225,123). The latter Patent teaches that such compositions may include a clot activator such as silica particles. The effervescence will assist in distributing the clot activator throughout a collection vessel to promote rapid blood coagulation prior to removal of serum. Such additives can be made in solid forms (including tablets) for addition to tubes containing blood samples.
It is known that the presence of calcium ions in a wound bed will promote healing and this has led to treatments involving topical application of calcium to wounds, such as through use of calcium alginate dressings. Kawai et al.13 prepared 50-200 nm nanoparticles from collagen and calcium chloride for intravenous injection. They found better wound healing in an open wound mouse model after injection of the calcium-based nanoparticles as compared to intravenous injection of calcium chloride. They also compared results following topical administration of calcium chloride and calcium-based nanoparticles directly to open wounds.
Consistent with results obtained with calcium containing dressings, topical administration of calcium chloride accelerated healing but topical administration of the calcium-based nanoparticles did not significantly change wound healing rate.
Foaming hemostatic and adhesive fibrin preparations that may contain calcium ions are also known, such as those disclosed in WO2000/038752 and WO2011/123346. Spreading of components that provide for a fibrin matrix results from the foaming action. The foaming results from generation of CO2. Neither reference discloses particles that propel themselves. For example, WO2011/123346 discloses the generation of CO2 by mixing a solution containing fibrin scaffold components and sodium bicarbonate with an acidic solution. WO2000/038752 discloses a composition in powder or granular form that contains components for forming a fibrin matrix, together with a carbonate and a physiologically acceptable organic acid. The latter composition effervesces upon contacting moisture.